The goal is to confirm, characterize and identify a factor(s) released from specific tumor cells in vivo to the circulation and in vitro to culture medium in order to probe its potential as a general assay for the presence of transformed and/or malignant cells. By use of a biochemical assay factors which were low or absent in normal rat plasma were detected in blood plasma of tumor-bearing rats. The plasma factor is detectable within 48 hours of treatment of rats with a carcinogenic regimen of dimethyl nitrosamine or thiocacetamide. The activity in this initial transient phase, which is maximal at 3 weeks, was followed by a progressive increase in activity, which after 8 to 10 months, attained a level 5 to 6 times the initial increase. The latter initial increase appears to parallel tumorigenesis. The activity increases slightly during the early phase of liver regeneration or CC14 treatment, with normalization of plasma activity within 15 days. The appearance of the factor in rat circulation coincides with that of a Mr 60,000 phosphoprotein. A factor with similar biochemical activity was detected in the plasma of (in excess of) 100 cancer patients tested with cancers at 33 different sites, and in conditioned culture medium. The factor from pooled cancer patient plasma had a molecular weight of Mr 70,000 on Sepharose 6B chromatography. The factor was low and absent in nonconditioned medium, in the plasma of normal controls and in patients free of active cancer (i.e., leukemia patients in remission). The activity chromatographing in the 60 to 70 dalton region appears to be very specific for transformed cells and for cells exposed to carcinogens. Experiments just completed strongly suggest that the 60 Kd factor is an oncofetal form of the messenger RNA transport protein.